At present, therapy for established postmenopausal osteoporosis is limited to antiresorptive agents which will retard further bone loss. No significant increment in bone mass would be expected from such treatment beyond recouping some of the resorption space as activation frequency declines. Preliminary data have suggested that (1-34) hPTH might increase cancellous bone mass, but no controlled studies have been performed. Potential detrimental effects on cortical bone, suggested in studies of primary hyperparathyroidism, have not been excluded. Further, stimulation of calcium absorption by addition of 1,25(OH)2D3 appeared necessary for the PTH effect on bone mass. Since estrogens improve calcium absorption and appear to have synergistic effects with PTH on local modulators of bone formation, but antagonistic effects to PTH on mediators of resorption, the present application proposes to test the hypothesis that PTH will increase bone mass in estrogen-treated individuals. These efforts are a direct expansion of a SCOR award designed to determine if bone mass can be increased in osteoporotic patients already established on approved antiresorptive therapy. The current proposal conforms closely to the original goals of the Center grant, and extends the aims of Projects 1 and 2 of the original application, which sought to evaluate interactions between parathyroid hormone, sex steroids and local mediators of bone remodeling in in vitro models and animal models of bone loss.